title: Identification of cell cycle-regulated genes periodically expressed in U2OS cells and their regulation by FOXM1 and E2F transcription factors.
abstract: We identify the cell cycle-regulated mRNA transcripts genome-wide in the osteosarcoma-derived U2OS cell line. This results in 2140 transcripts mapping to 1871 unique cell cycle-regulated genes that show periodic oscillations across multiple synchronous cell cycles. We identify genomic loci bound by the G2/M transcription factor FOXM1 by chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) and associate these with cell cycle-regulated genes. FOXM1 is bound to cell cycle-regulated genes with peak expression in both S phase and G2/M phases. We show that ChIP-seq genomic loci are responsive to FOXM1 using a real-time luciferase assay in live cells, showing that FOXM1 strongly activates promoters of G2/M phase genes and weakly activates those induced in S phase. Analysis of ChIP-seq data from a panel of cell cycle transcription factors (E2F1, E2F4, E2F6, and GABPA) from the Encyclopedia of DNA Elements and ChIP-seq data for the DREAM complex finds that a set of core cell cycle genes regulated in both U2OS and HeLa cells are bound by multiple cell cycle transcription factors. These data identify the cell cycle-regulated genes in a second cancer-derived cell line and provide a comprehensive picture of the transcriptional regulatory systems controlling periodic gene expression in the human cell division cycle.
authors.affiliation: Department of Genetics, Geisel School of Medicine at Dartmouth, Hanover, NH 03755 Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305.
authors.forename: Gavin D
authors.initials: GD
authors.lastname: Grant
authors.forename: Lionel
authors.initials: L
authors.lastname: Brooks
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Zhang
authors.forename: J Matthew
authors.initials: JM
authors.lastname: Mahoney
authors.forename: Viktor
authors.initials: V
authors.lastname: Martyanov
authors.forename: Tammara A
authors.initials: TA
authors.lastname: Wood
authors.forename: Gavin
authors.initials: G
authors.lastname: Sherlock
authors.forename: Chao
authors.initials: C
authors.lastname: Cheng
authors.forename: Michael L
authors.initials: ML
authors.lastname: Whitfield
mesh_terms: D002453:Cell Cycle / Q000235:genetics; D047369:Chromatin Immunoprecipitation; D050684:E2F Transcription Factors / Q000378:metabolism*; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D018816:Genes, cdc; D006367:HeLa Cells; D006801:Humans; D005810:Multigene Family; D011485:Protein Binding / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic
chemical_list: D050684:E2F Transcription Factors; C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger